ABSTRACT Alzheimer’s disease and related dementias (ADRD) affect 5.6 million Americans at an annual cost of $157 billion. Three million Americans have late-stage ADRD with suffering caused by progressive dependency and distressing symptoms. Family caregivers experience extraordinary physical, emotional and financial strain. Hospitalizations for acute illnesses are common in late-stage ADRD, with worsened symptoms and distressing decisions about goals of care and intensive treatments. Hospitalizations also present a unique opportunity for dementia-specific palliative care to address suffering and reduce burdensome treatments, since 72% of hospitals have palliative care teams. Palliative care improves symptom control and quality of life in serious illnesses, but has never been adapted and tested for the unique needs of late-stage ADRD. We therefore developed the ADRD Palliative Care (ADRD-PC) program. Using a novel rapid screening system, we randomized 62 dyads of hospitalized patients with late-stage ADRD and their family caregivers to the ADRD-PC program vs education control. Intervention dyads received i) dementia-specific palliative care, ii) standardized caregiver education, and iii) transitional care delivered by an interdisciplinary palliative care team; control dyads received educational material on dementia caregiving. The ADRD-PC program was well- accepted, and resulted in significant improvements in use of hospice, symptom management, caregiver communication about prognosis and goals of care, new advance directives, and “Do Not Hospitalize” orders. The necessary next step to advance the science of dementia-specific palliative care is an adequately powered RCT of the efficacy of the ADRD-PC program to improve patient and family centered outcomes. Our research objective is to conduct a multi-site efficacy RCT of the ADRD-PC program. We will enroll 424 dyads of hospitalized patients with late-stage ADRD and family caregivers at 4 geographically diverse member sites of the Palliative Care Research Cooperative group. Our Specific Aims are: Aim 1: To conduct a multi-site RCT of the ADRD-PC program of dementia-specific palliative and transitional care (intervention arm) vs publicly available educational material for dementia caregivers (control arm) to compare 60-day hospital transfers (hospitalization and emergency room visits) for persons with late-stage ADRD (primary outcome). Aim 2: To compare patient-centered secondary outcomes between intervention and control arms: a) symptom treatment; b) symptom control; c) post-acute use of community palliative care or hospice; and d) new nursing home transitions. Aim 3: To compare caregiver-centered secondary outcomes between intervention and control arms: a) communication about prognosis and goals of care; b) shared decision-making; and c) caregiver distress. IMPACT: ADRD-PC has the potential to reduce suffering for millions of persons with late-stage ADRD.